Clinical Thoughts and Cases of Jianpi Yishen Sechang Decoction Combined with Acupuncture in the Treatment of Functional Diarrhea

Functional diarrhea(FDr)accounts for a relatively high proportion of digestive diseases.It is an infection that is not accompanied by abdominal pain and shows negative results in laboratory tests for bacteria and viruses.The main symptoms are persistent or recurrent discharge of watery and soft stools.The course of the disease is prolonged and recurring,and the treatment cost is higher and greatly affects the patient’s daily life.The incidence rate has a gradual increase in the trend.Its pathogenesis is complex where Western medicine is mostly used in symptomatic drug treatment.The treatment can be fast-acting and effective in relieving diarrhea.However,the long-term use of Western medicine poses a high risk in terms of side effects and a high chance of recurring upon stopping medication.At the same time,some diarrhea patients show the existence of drug-resistant strains of bacteria,and the overall efficacy of the drug is limited.Chinese medicine is mild and able to provide excellent treatment of diarrhea.With its lower price and cost,most families can afford it.Fengliang Tian,director of traditional Chinese medicine,implemented the“needle and medicine”method,which combines medicine and acupuncture,involving the usage of Jianpi Yishen Sechang Decoction and acupuncture in the treatment of functional diarrhea.The method has a low price,fewer side effects,is easy to accept,and can significantly reduce the recurrence rate with high efficacy.The study would like to share the clinical thinking and cases as follows to provide ideas and methods for the treatment of functional diarrhea by traditional Chinese medicine.

Exploring the mechanism of Yishen Daluo decoction in the treatment of multiple sclerosis based on network pharmacology and in vitro experiments

Objective:To explore the mechanism and related active components of Yishen Daluo decoction(YSDLD)in treating multiple sclerosis(MS).Methods:Targets of YSDLD were collected through the TCMSP,Chemistry,and TCMID databases.The MS targets were collected through OMIM,DrugBank,Gencards,TTD,and Pharmgkb databases.We built“componentetarget”network diagrams and proteineprotein interaction(PPI)diagrams and performed topological analysis.The targets were subjected to GO and KEGG enrichment analysis.Molecular docking verification was conducted on selected targets and molecules.Finally,in vitro experiments were con-ducted.BV2 cells were induced by lipopolysaccharide for model establishment.CCK8 experiment was conducted to explore the effect of YSDLD and RT-qPCR technology was used to explore the expression of key targets.Results:There were 184 active components in YSDLD and 898 targets of its action.There were 940 MS targets,and 215 targets were shared by YSDLD and MS.According to the“componentetarget”diagram,the top five key components included quercetin,kaempferol,beta-sitosterol,stigmasterol,and nar-ingenin.IL-6,IL-1 b,TNF-α,AKT1,and VEGFA were the important targets identified by PPI network to-pology analysis.A total of 564 functions were identified by GO enrichment analysis(P<0.01),mainly involving inflammatory response,hypoxia response,plasma membrane,neuronal cell body,protein phosphatase binding,and cytokine activity.KEGG enrichment analysis enriched 98 pathways(P<.01).YSDLD at the concentration of 20 m g/mL had no effect on BV2 cells.RT-qPCR indicated that YSDLD at the concentrations of 15 m g/mL and 20 m g/mL alleviated LPS-induced inflammatory injury and lowered the content of inflammatory factors(P<0.05).Conclusion:In this paper,the network pharmacology and in vitro experiments were used to explore the potential mechanism of YSDLD in treating MS.The research provides a good basis for the development of YSDLD and drugs for MS in future.

Meta analysis and data mining of the method of yishenhuoxue in the treatment of nonproliferative diabetic retinopathy

Objective:To evaluate the efficacy and safety of the method of Yishen Huoxue in the intervention of nonproliferative diabetic retinopathy(NPDR)by Meta analysis and explore the medication regularity of Chinese Medicine(TCM)based on data mining.Methods:The related literature of TCM in the treatment of NPDR published in CNKI,VIP,WF,PubMed,the Cochrane Library,SinoMed,Embase were collected.The quality of the included literature was evaluated with reference to the Cochrane System Evaluators'Handbook,and statistical analysis was performed by applying Revman 5.4.1 software.After normalization of the Chinese medicine names,association rule analysis was performed by using SPSS Modeler 18,and then Cytoscape was used to produce complex network diagrams.Results:20 RCTs were included.Meta-analysis results showed that the method of Yishen Huoxue or Yishen Huoxue combined with western medicine were better than the control group in improving the total clinical efficiency[RR=1.21,95%CI(1.16,1.27),P<0.00001],TCM symptom efficacy[RR=1.28,95%CI(1.18,1.39),P<0.00001],and visual acuity[MD=0.11,95%CI(0.05,0.17),P=0.0001],HDL-C[MD=0.14,95%CI(0.03,0.25),P=0.02];reducing the number of fundus hemangiomas[MD=-3.51,95%CI(-5.73,-1.28),P=0.002],hemorrhagic spot area[MD=-0.70,95%CI(-0.95,-0.46),P<0.00001],CMT[MD=-35.31,95%CI(-55.47,-15.14),P=0.0006],FBG[MD=-0.39,95%CI(-0.72,-0.05),P=0.02],LDL-C[MD=-0.36,95%CI(-0.64,-0.08),P=0.01],whole high blood viscosity[MD=-0.43,95%CI(-0.75,-0.12),P=0.006],plasma viscosity[MD=-0.36,95%CI(-0.67,-0.06),P=0.02]and fibrinogen[MD=-0.50,95%CI(-0.81,-0.19),P=0.002].The differences were statistically significant.The 20 recipes entered involved a total of 70 herbal medicines.It is analyzed that the high-frequency drugs and the core drugsare gou qi,san qi,dan shen,haung qi,sheng di huang,et al.The association rule analysis summarizes the commonly used pairs including:sheng di huang-san qi,sheng di huang-gou qi,et al.Conclusions:Compared with western medicine treatment alone,the method of Yishen Huoxue or Yishen Huoxue combined with western medicine produce better effects,but it still needs to be verified by higher quality clinical studies.

Bufei Yishen granules suppress oxidative stress in rats with chronic obstructive pulmonary disease via Nrf2 signaling

OBJECTIVE To explore the antioxidant effect of Bufei Yishen granules on chronic obstructive pulmo⁃nary disease(COPD)and investigate its underlying mechanism.METHODS Forty-eight rats were randomly divided into normal,model,Bufei Yishen granules(BY)and N-acetylcysteine(NAC)groups,12 rats in each group.The stable COPD rat model was duplicated by using repeated cigarette smoke exposure combined with Klebsiella bacterial infection for 12 weeks(week 1-12),and the corresponding drugs were administered for the next 8 weeks(week 13-20).Minute volume(MV),tidal volume(TV)and peak expiratory flow(PEF)were measured by whole body plethysmography(WBP)system every 4 weeks.Before sacrificed,forced vital capacity(FVC)and forced expiratory volume 0.1(FEV0.1)were measured byPFT system.The pathological changes of lung tissue were observed by pathological techniques.Heme oxygenase 1(HO-1),superoxide dismutase 1(SOD1)and Nrf2 in lung tissue were measured by immunohisto-hemical method.The total anti oxidizing capability(T-AOC),lipid peroxide(LPO)in rat serum were measured.The expression of Nrf2,HO-1 andγ-glutamyl cysteine synthetase(γ-GCS)mRNA in lung tissue was detected by quantitative polymerase chain reac⁃tion(qPCR).The protein expression of Keap1,Nrf2 and HO-1 in lung tissue were detected by Western blotting.RESULTS①Lung function:compared with normal group,the MV in model group was significantly decreased at week 8(P<0.01),the TV and PEF were significantly decreased at week 4(P<0.01).At week 20,compared with model group,MV,TV,and PEF in the BY and NAC groups were significantly increased(P<0.01);compared with the NAC group,MV,TV,and PEF in BY group were significantly increased(P<0.01).At the end of week 20,the FVC and FEV0.1 in model group were significantly lower than that in normal group(P<0.01).Compared with model group,the FVC and FEV0.1 in the BY and NAC groups were significantly increased(P<0.05).②Oxidative indexes:Compared with Normal group,T-AOCin serum was significantly decreased in Model group,while LPO was significantly increased(P<0.01).Compared with the Model,T-AOC in BY and NAC groups was significantly increased(P<0.01),and the LPO was significantly decreased(P<0.05,P<0.01).There were no difference between the BTG and NAC.③Nrf2 signaling:Nrf2 and HO-1 in lung tissue were mainly expressed in the cytoplasm and part of the nucleus of alveolar epithelial cells.SOD1 protein was mainly distributed in bronchial epithelial cells and alveolar septa.Compared with normal group,the expression of Nrf2 in the model group was increased(P<0.01),and HO-1 and SOD1 were decreased(P<0.01).Compared with the model,the expression of Nrf2 in the BY group was significantly increased(P<0.05),and HO-1 and SOD1 in BY and NAC groups were both increased(P<0.01).Compared with the NAC group,the expression of HO-1 in BY group was increased(P<0.01).Compared with normal group,the Nrf2 mRNA expression of lung tissue in the model was significantly increased(P<0.01),the HO-1 andγ-GCS mRNA was decreased(P<0.01).Compared with model group,the Nrf2,HO-1,andγ-GCS mRNA in the BY group were increased(P<0.01),the HO-1,andγ-GCS mRNA in NAC group were increased(P<0.01).Compared with normal group,the Nrf2 protein expression of lung tissue in the model group was significantly increased(P<0.01),and HO-1 protein expression was significantly decreased(P<0.01).Compared with the model,the Nrf2 and HO-1 protein in NAC and BY groups was significantly increased(P<0.01).CONCLUSION Bufei Yishen gran⁃ules has beneficial curative effect in COPD rats,and has the same antioxidation effect as NAC,the mechanism may be involved in upregulating Nrf2 signaling.

Effects of Suoquan Yishen Formula on Mice with Diabetic Nephropathy (DN)

[Objectives]The purpose of this paper was to study the effects of Suoquan Yishen formula on mice with diabetic nephropathy(DN).[Methods]The mice were randomly divided into normal group,model group,irbesartan group,and high and low-dose Suoquan Yishen formula groups.The blood glucose level,BUN,Scr excretion and GSH activity and CAT activity were detected.[Results]The blood glucose levels of mice in the irbesartan group and high and low-dose Suoquan Yishen formula groups decreased.The BUN,PRO and Scr levels were higher and the GSH and CAT activity was lower in the model group compared with the normal group.After administration of Suoquan Yishen formula,the BUN,PRO and Scr levels of the DN mice decreased significantly,and the GSH and CAT activity increased significantly.[Conclusions]Suoquan Yishen formula can reduce blood glucose level,reduce PRO,BUN and Scr levels,and increase CAT and GSH activity in DN mice,thus protecting the ND mice.

Pharmacological mechanisms of Yishen Xingyang capsule in the treatment of oligoasthenospermia in rats

Objective:To investigate the therapeutic effects and pharmacological mechanisms of Yishen Xingyang capsule(YXC)in oligoasthenospermia(OA)rats.Methods:Forty-eight male SpragueeDawley rats were randomly divided into eight groups of six rats each:normal control(NC);model control(MC);three different positive drug(PD);and low-,medium-,and high-dose YXC groups.A rat model of OA was established by administering glucosides of Tripterygium wilfordii Hook.F(GTW).After YXC administration,penile erectile function was observed.The epididymis,blood,and testes of the rats were harvested for analysis of sperm quality,sex hormone levels,mitochondrial membrane potential,and the transforming growth factor(TGF)-b1/Smad signaling pathway.Results:Compared with that in the MC group,penile erectile function in the YXC groups and three PD groups increased(all P<.01).Moreover,sperm quality in the YXC groups and three PD groups improved(all P<.001).The levels of testosterone,follicle stimulating hormone,and luteinizing hormone in the three PD and YXC groups increased(all P<.05).The mitochondrial membrane potential in the three PD and YXC groups significantly improved(all P<.001).Furthermore,the YXC and three PD groups showed decreased TGF-b1 expression(all P<.05)compared with the MC group.The high-dose YXC group and three PD groups improved Smad2 and Smad4 expression(all P<.05).Conclusion:YXC improved penile erectile function and sperm quality in OA rats,and the underlying mechanism included increase in sex hormones,inhibition of sperm apoptosis,and regulation of the TGFb1/Smad signaling pathway.Meanwhile,this study provides a new effective drug option for the treatment of OA,which is beneficial to male reproductive health and social harmony.

The effects of Yishen Qutong granula on pain sensitization and bone destruction of rats with bone cancer pain

Objective:To study the effects of Yishen Qutong granula on pain sensitization and bone destruction of rats with bone cancer pain.Methods:Walker256 cells were passaged in ascites and injected into the tibia of female Wistar rats to prepare the bone cancer pain model.On the 14th day after model establishment,60 rats were randomly divided into model group,sham-operated group,Yishen Qutong granula low,middle,high dose group and tramadol hydrochloride positive control group.After continuous administration for 14 days,the mechanical pain threshold,thermal threshold and weight-bearing difference of both hind limbs were observed.Results:Compared with the model group,Yishen Qutong groups increased the mechanical pain threshold,thermal pain threshold and reduced the weight difference of both hind limbs(P<0.05).Compared with the positive drug group,there was no significant difference in increasing the mechanical pain threshold and thermal pain threshold of rats in the medium dose group of Yishen Qutong(P>0.05),and Yishen Qutong granula significantly reduced the weight-bearing difference of hind limbs in all groups(P<0.05).Conclusion:Yishen Qutong granula can relieve pain sensitization and alleviate bone damage in rats with bone cancer pain.

Protective effects of Yishen Sanjie Huayu compound on the renal artery disease in rats with IgA nephropathy through ERK/NF-κB pathway

Objective:To observe the effect of Yishen Sanjie Huayu compound prescription on ERK/NF-κB signaling pathway in IgA nephropathy(IgAN)rats,and explore its effect on preventing and treating IgA nephropathy intrarenal arteriole disease.Methods:Fifty-five male SD rats were randomly divided into blank group,model group,ShenfukangⅡcapsule group and Losartan potassium tablet group.Bovine serum albumin(BSA)was used for intragastric administration and carbon tetrachloride(CCl4).IgAN rat model was established by subcutaneous injection and lipopolysaccharide(LPS)tail vein injection.ShenfukangⅡcapsule group and Losartan potassium tablet group were given each drug suspension 2ml/head/d one week after modeling Gavage was started.The blank group and the model group were given an equal volume of normal saline.The 24h urine protein(UTP)of the rats was measured at 4,8,and 12 weeks after the administration,and the blood creatinine(SCr)was measured after 12 weeks.,urea nitrogen(BUN),aldosterone(ADS),angiotensinⅡ(AngⅡ),immunohistochemical Envi-sion System two-step method to detect vascular endothelial growth factor(VEGF)and human matrix in the whole rat kidney and small artery area The expression of metalloproteinase-9(MMP-9),proliferating cell nuclear antigen(PCNA),extracellular regulatory protein kinase(ERK)1/2,nuclear transcription factor-κB(NF-κB),and the small arteries of rat kidney tissue The intima,media,vessel wall/vascular outer diameter value.Results:Compared with the model group,the expressions of VEGF,MMP-9,PCNA,ERK1/2 and NF-κB in kidney tissues of the ShenfukangⅡcapsule group and the Losartan potassium tablet group decreased(P<0.05),24hUTP and SCr,BUN level decreased(P<0.05),kidney tissue damage was alleviated;intima and vessel wall/vascular outer diameter values were significantly reduced(P<0.01),there was no significant difference in ADS between the groups.The AngⅡof the Tanpotassium tablets group was lower than that of the model group(P<0.05).Conclusion:Yishen Sanjie Huayu compound can inhibit the ERK/NF-κB signaling pathway in rats with IgA nephropathy,reduce the levels of VEGF,MMP-9,PCNA,ERK1/2,NF-κB,and inhibit intrarenal arteriole vascular endothelial cells Proliferate and reduce kidney damage.

Influence of Yishen Guben Qutong decoction combined with menatetrenone soft capsule on bone metabolism,bone conversion index and clinical efficacy in osteoporosis patients

Objective:To observe the effect of tetradecylene naphthalene soft capsule combined with Yishen Gubenyutong Decoction on bone metabolism and bone turnover in patients with osteoporosis and its clinical efficacy.Methods:A total of 100 patients with primary osteoporosis(all were treated by our hospital from February 2017 to June 2018)were divided into two groups.The control group(50 cases)was given to menatetrenone capsules.Treatment,observation group(50 cases)combined with Yishen Gubenqiaotongtong on the basis of the treatment of the control group,6 months for a course of treatment.The bone metabolic markers,bone mineral density changes and clinical efficacy were measured before and after treatment.Results:The total effective rate of the observation group was higher than that of the control group.After treatment,the observation group showed serum calcium(Ca),serum alkaline phosphatase(ALP)and typeⅠcollagen.The level of cross-linked C-terminal peptide(CTX-1)was lower than that of the control group.After treatment,the osteocalcin(OC)in the observation group was higher than that in the control group,and the bone mineral density(BMD)of lumbar vertebrae L2-4,femoral neck and femur trochanter in the observation group were higher than those in the control group.Conclusion:Menatetrenone soft capsule combined with Yishen Gubenyutong Decoction has good clinical effect on osteoporosis patients and it is worth further promotion in clinic.

Effects of Danqi Yishen Capsule on Blood Lipid Levels and Hemorheological Indicators of Hyperlipidemia Patients

Objective: To explore the effects of Danqi Yishen Capsule (Danqi Capsule for Tonifying Kidney) on blood lipid levels and hemorheological indicators of hyperlipidemia patients. Methods: A total of 96 patients with hyperlipidemia were randomly divided into the control group and observation group of 48 cases respectively. The control group was given by simvastatin in oral administration of 10 mg half an hour after dinner, once a day, while the observation group based on the treatment of the control group, was orally given Danshen Yishen Capsule of three capsules each time, three times a day. The treatment of both groups lasted for two months. Then the comparison focused on blood lipid levels, hemorheological indicators, and adverse reactions between both groups before and after the treatment. Results: There was no significant difference in blood lipid levels and hemorheological indicators between both groups before the treatment (P > 0.05). The symptoms of both groups were significantly improved after the treatment, and the difference before and after the treatment was statistically significant (P < 0.05), and the difference between both groups was also statistically significant (P < 0.05). There was no significant difference in the incidence rate of adverse reactions between both groups (P > 0.05). Conclusion: Danqi Yishen Capsule has a significant value in clinical applications, which can optimize clinical efficacy, improve blood lipid levels and hemorheological indicators of hyperlipidemia patients, as well as reduce the probability of adverse reactions in patients.

Exploring the mechanism of Pinggan Yishen granules in the treatment of hypertension and insomnia through network pharmacology and molecular docking

Background:Hypertension is closely related to insomnia.Pinggan Yishen(PGYS)Granule is an effective compound medicine for treating hypertension and insomnia.In this study,we aimed to systematically explain the potential mechanism of PGYS granules in the treatment of hypertension and insomnia using network pharmacology and molecular docking techniques.Methods:Potential targets accounted for hypertension and insomnia were obtained from OMIM,GeneCards,and DrugBank databases.We used the Batman-TCM database to query natural compounds and potential targets associated with PGYS granules.According to the localization results of PGYS granules and potential target genes of disease,the protein-protein interaction network was constructed.The tissue and subcellular distribution information for key proteins are visualized.Used KOBAS3.0 to enrich KEGG pathways and GO biological processes.Molecular docking was used to verify relationships between core compounds and proteins.Results:The comorbid mechanism of hypertensive insomnia is mainly related to disorders of neurotransmitter regulation,imbalance of the renin-angiotensin-aldosterone system(RAAS),abnormal metabolism including cytokine secretion and lipid metabolism.The potential therapeutic mechanisms of PGYS granules include the regulation of neurotransmitters,lipid metabolism and inflammatory response.CACNA1C,adrenergic receptors,cytochrome P450 family and muscarinic cholinergic receptors may be the key targets of PGYS granules.Conclusion:Hypertension and insomnia are related in mechanisms.PGYS granules may play a therapeutic role in hypertension and insomnia by regulating neurotransmitters,lipid metabolism and inflammatory response.

Network Pharmacology-based Analysis on Determining the Mechanisms of Yishen Qutong Granules(益肾祛痛颗粒)in Alleviating Cancer-related Fatigue

Cancer-related fatigue(CRF)is associated with cancer-related anemia(CRA).As the common comorbidities of cancer,both of them can seriously affect the quality of patient life.Yishen Qutong Granules(益肾祛痛颗粒,YSQTG)have achieved good curative effects in the treatment of CRA.However,the mechanism of whether it can alleviate CRF needs further confirmation.We used network pharmacology and molecular docking to investigate the molecular mechanism and the effective compounds of the prescription.Through the analysis and research in this paper,we obtained 76 effective compounds and 76 drug-disease intersection targets to construct a network,indicating that quercetin,luteolin,baicalein,β-sitosterol and stigmasterol were possibly the most important compounds in YSQTG.The key targets of YSQTG for CRF were mainly enriched in IL-17 and TNF pathways.816 GO entries and 113 pathways were obtained by GO and KEGG enrichment,respectively,which proved that YSQTG might have a comprehensive therapeutic effect on CRF mainly through regulating IL-17,TNF,MAPK,NF-κB and chemokines,as well as cholinergic synapse and 5-HT synapse pathways.The results of molecular docking showed thatβ-sitosterol and stigmasterol could form PI-Alkyl or Alkyl hydrophobic interactions with CXCL8 and ESR1 at residues LEU25,ARG26,PHE65,ALA69 and LEU346,ALA350,LEU391,PHE404,LEU525,VAL533,respectively.In conclusion,the therapeutic effect of YSQTG on CRF is based on the comprehensive pharmacological effect of multicomponent,multitarget,and multichannel pathways.This study provides a theoretical basis for further experimental research.

Network Pharmacology and in vitro Experimental Veriflcation on Intervention of Quercetin, Present in Chinese Medicine Yishen Qutong Granules, on Esophageal Cancer

Objective: To explore the potential mechanism of Yishen Qutong Granules(YSQTG) for the treatment of esophageal cancer using network pharmacology and experimental research. Methods: The effective components and molecular mechanism of YSQTG in treating esophageal cancer were expounded based on network pharmacology and molecular docking. The key compound was identified by high-performance liquid chromatography and mass spectrometry(HPLC-MS) to verify the malignant phenotype of the key compounds in the treatment of esophageal cancer. Then, the interaction proteins of key compounds were screened by pull-down assay combined with mass spectrometry. RNA-seq was used to screen the differential genes in the treatment of esophageal cancer by key compounds, and the potential mechanism of key compounds on the main therapeutic targets was verified. Results: Totally 76 effective compounds of YSQTG were found, as well as 309 related targets, and 102 drug and disease interaction targets. The drug-compound-target network of YSQTG was constructed, suggesting that quercetin, luteolin, wogonin, kaempferol and baicalein may be the most important compounds, while quercetin had higher degree value and degree centrality, which might be the key compound in YSQTG. The HPLC-MS results also showed the stable presence of quercetin in YSQTG. By establishing a protein interaction network, the main therapeutic targets of YSQTG in treating esophageal cancer were Jun proto-oncogene, interleukin-6, tumor necrosis factor, and RELA proto-oncogene. The results of cell function experiments in vitro showed that quercetin could inhibit proliferation, invasion, and clonal formation of esophageal carcinoma cells. Quercetin mainly affected the biological processes of esophageal cancer cells, such as proliferation, cell cycle, and cell metastasis. A total of 357 quercetin interacting proteins were screened, and 531 genes were significantly changed. Further pathway enrichment analysis showed that quercetin mainly affects the metabolic pathway, MAPK signaling pathway, and nuclear factor kappa B(NF-κB) signaling pathway, etc. Quercetin, the key compound of YSQTG, had stronger binding activity by molecular docking. Pull-down assay confirmed that NF-κB was a quercetin-specific interaction protein, and quercetin could significantly reduce the protein level of NF-κB, the main therapeutic target. Conclusion: YSQTG can be multi-component, multi-target, multi-channel treatment of esophageal cancer, it is a potential drug for the treatment of esophageal cancer.

Clinical Observation of the Treatment of Myelodysplastic Syndrome Mainly with Qinghuang Powder(青黄散)

Objective： To observe the clinical effectiveness of Qinghuang Powder （青黄散, QHP） combined with Bupi Yishen Decoction （补脾益肾汤 BPYS） in treating myelodysplastic syndrome （MDS）, and its relationship with France, America, and Britain （FAB） type, international prognosis scaling system （IPSS） risk, and chromosome karyotype. Methods： There were 124 MDS patients subjected to the tests. By FAB typing, 91 patients were typed as refractory anemia （RA） type and 33 as refractory anemia with excess of blasts （RAEB） type; by IPSS scale, 21 were sorted to low risk, 77 to moderate risk I, 20 to moderate risk ]], and 6 to high risk; 78 of them had normal chromosome and 46 with abnormal chromosome, including 26 of trisomy 8. All patients were treated with QHP＋BPYS, and the changes of peripheral blood figure and bone marrow were observed. Results： After treatment, the general effective rate was 72.58% （90/124）, which in the patients of RA type was 80.22% （73/91） and in RAEB type 51.52% （17/33）. The former was better than that in the later （P〈0.01）. For the analysis in the patients of different IPSS risk degrees, the effective rate was 95.24% （20/21） in the low- risk group, 72.73% （56/77） in moderate risk I, 65.00% （13/20） in moderate-risk 11, and 16.67% （1/6） in high- risk group. Those in the first two groups were superior to that in the latter two （P〈0.01）. The effective rate was 79.49% （61/78） in the patients with normal chromosome and was 60.87% （28/46） in the patients with abnormal chromosome, showing a significant difference between them. While in the patients of trisomy 8, it was 73.08% （19/26）, which was parallel to that in the patients with normal chromosome. Conclusion： The effectiveness of QHP＋BPYS comprehensive therapy for MDS is unquestionably good, and it is markedly correlated with the FAB type and IPSS risk degree of the disease, as well as the normality of chromosome in the patient.

Effect of Qinghuang Powder(青黄散) Combined with Bupi Yishen Decoction(补脾益肾方) in Treating Patients with Refractory Cytopenia with Multilineage Dysplasia through Regulating DNA Methylation

Objective: To explore the effect of Qinghuang Powder(QHP, 青黄散) combined with Bupi Yishen Decoction(BPYS, 补脾益肾方)on myelodysplastic syndromes(MDS) patients with refractory cytopenia with multilineage dysplasia(RCMD) and determine the change of DNA methylation in MDS-RCMD patients after the treatment of Chinese medicine formula. Methods: All 308 MDS-RCMD patients were treated with QHP combined with BPYS for 2 months at least, absolute neutrophil count(ANC), hemoglobin(Hb), platelets(PLT), primitive bone marrow cells and chromosome karyotype were chosen as the main evaluation indexes to analyze the treatment effect according to criteria from the MDS International Working Group. Then 43 bone marrow samples from 15 MDS-RCMD patients and 28 healthy donors were obtained for the examination of DNA methylation.Gene Ontology(GO) and Pathway analysis were applied to analyze the methylation data. Results: The overall MDS response rate to QHP was 61.68%(190/360) including hematologic improvement-neutrophil(HI-N) or hematologic improvement-erythroid(HI-E) or hematologic improvement-platelet(HI-P). Patients with anemia had a better response rate than patients with neutropenia or thrombocypenia(55.88% vs 31.54% or 55.88%vs. 36.9%). The DNA methylation microarray analysis disclosed that 4,257 hypermethylated genes were demethylated upon the treatment with QHP and BPYS. GO analysis and Pathway analysis showed that these demethylated genes were involved in a lot of tumor-related pathways and functions. Conclusions: QHP combined with BPYS could effectively treat MDS-RCMD patients through hematologic improvement(HI-N, HI-P or HI-E)and PLT and RBC transfusion independence due to the demethylation, thereby providing another choice for the treatment of patients with MDS-RCMD.

Effective-constituent compatibility-based analysis of Bufei Yishen formula, a traditional herbal compound as an effective treatment for chronic obstructive pulmonary disease

Objective:Critical effective constituents were identified from Bufei Yishen formula(BYF),a traditional herbal compound and combined as effective-constituent compatibility(ECC)of BYF I,which may have potential bioactive equivalence to BYF.Methods:The active constituents of BYF were identified using four cellular models and categorised into Groups 1(Bufeiqi),2(Bushen),3(Huatan)and 4(Huoxue)according to Chinese medicinal theory.An orthogonal design and a combination method were used to determine the optimal ratios of effective constituents in each group and the ratios of‘‘Groups 1 to 4"according to their pharmacological activity.We also comprehensively assessed bioactive equivalence between the BYF and the ECC of BYF I in a rat model of chronic obstructive pulmonary disease(COPD).Results:We identified 12 active constituents in BYF.The numbers of constituents in Groups 1 to 4 were 3,2,5 and 2,respectively.We identified the optimal ratios of effective constituents within each group.In Group1,total ginsenosides:Astragalus polysaccharide:astragaloside IV ratio was 9:5:2.In Group 2,icariin:schisandrin B ratio was 100:12.5.In Group 3,nobiletin:hesperidin:peimine:peiminine:kaempferol ratio was4:30:6.25:0:0.In Group 4,paeoniflorin:paeonol ratio was 4:1.An orthogonal design was then used to establish the optimal ratios of Group 1,Group 2,Group 3 and Group 4 in ECC of BYF I.The ratio for total ginsenosides:Astragalus polysaccharide:astragaloside IV:icariin:schisandrin B:nobiletin:hesperidin:peimine:paeoniflorin:paeonol was determined to be 22.5:12.5:5:100:12.5:4:30:6.25:25:6.25.A comprehensive evaluation confirmed that ECC of BYF I presented with bioactive equivalence to the original BYF.Conclusion:Based on the ECC of traditional Chinese medicine formula method,the effective constituents of BYF were identified and combined in a fixed ratio as ECC of BYF I that was as effective as BYF itself in treating rats with COPD.

Yishen Jiangzhuo Granules(益肾降浊冲剂) Affect Tubulointerstitial Fibrosis via A Mitochondrion-Mediated Apoptotic Pathway

Objective： To investigate the effect of Yishen Jiangzhuo Granules （益肾降浊冲剂 , YSJZG） on mitochondrial injury and regeneration and renal tubular epithelial cell apoptosis in chronic renal failure （CRF） rats and explore its mechanism from molecular pathology, gene, protein levels, and relative pathway. Methods： The CRF rat model was established using 5/6 nephrectomy. Sixty rats were randomly divided into six groups： sham-operation group, model （CRF） group, Niaoduqing Granules （尿毒清颗粒）-treated group [5 g/（kg.day）], low-, moderate-, and high-dose [L-YSJZG, M-YSJZG, H-YSJZG at 3, 6, and 9 g/（kg-day）] YSJZG-treated group （n=10 each）. The levels of serum creatinine （Scr）, blood urea nitrogen （BUN）, and 24-h urine protein were assessed after 10 weeks of treatment. The tubulointerstitial injury and collagen deposition were evaluated using periodic acid-schiff stain and Masson staining. Renal tubular epithelial cell apoptosis was assessed using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay, mitochondrial injury was observed using an electron microscope, and superoxide dismutase （SOD）, glutathione （GSH） and malondialdehyde （MDA） levels were assessed using chromometry. Transforming growth factor- 1 β（TGF-β 1） expression was assessed using immunohistochemistry. The expressions of Bax, Bcl-2, peroxisome proliferator-activated receptor γ coactivator-1 α （PGC-1α）, mitochondrial transcription factor A （Tfam）, mitogen-activated protein kinases （MAPK） phosphorylation were evaluated by Western blot. Results： YSJZG decreased the 24-h urine protein, BUN, Scr, remnant kidney weight-to-body weight ratio, renal tubular injury, deposition of collagen, and the apoptosis of renal tubular epithelial cells in a dose-dependent manner. YSJZG dose-dependently restored the number and structure of mitochondria and the expression of Tfam and PCG-1 α, up-regulated the expression of Bcl-2, and inhibited the expression of Bax. YSJZG also dose-dependently inhibited TGF- 13 1 expression, increased SOD and GSH activity, decreased the MDA level, and inhibited p38MAPK and pERK1/2 phosphorylation （all P〈0.01）. Conclusion： YSJZG improved the renal function in rats with CRF and inhibited the progression of tubulointerstitial fibrosis by dose-dependently alleviating mitochondrial injury, restoring the expression of Tfam and PCG-1α , and inhibiting renal tubular epithelial cell apoptosis through inhibiting activation of reactive oxygen species-MAPK signaling.

Study on Effect of Yishen Capsule (益肾胶囊) in Preventing Recurrence of Chronic Glomerulonephritis

Objective： To observe the effect of Yishen Capsule （益肾胶囊, YSC） on preventing the recurrence of chronic glomerulonephritis （CGN） and to explore its mechanism preliminarily. Methods： CGN patients were assigned to the treated group （61 cases） and the control group （48 cases） and all of them were orally administered with 4 mg of Perindopril twice a day, but 3 capsules of YSC, thrice a day, were given additionally to patients in the treated group. The therapeutic course for both groups was 18 months. The recurrence rate of CGN at the 6th, 12th, and 18th month in the two groups was observed and compared, and the changes of 24-h urinary protein quantity and T-lymphocyte subsets before and after treatment were observed as well. Results： （1） Comparison of recurrence rate between the two groups showed insignificant difference at the 6th month, but it did show significant difference at the 12th and the 18th month, which was significantly decreased in the treated group than in the control group （P〈0.05, P〈0.01）; （2） The 24-h urinary protein quantity at the 18th month decreased significantly in both groups （P〈0.05, P〈0.01）, but in the treated group was more significant （P〈0.01）; （3） T-lymphocyte subsets showed no obvious change in the control group after treatment （P〉0.05）, while in the treated group, it showed significant increase in CD3, CD4 and CD4/CD8 （P〈0.05 or P〈0.01） and significant decrease in CD8 （P〈0.05）, and also the difference after treatment in T-lymphocyte subsets between the two groups was significant （P〈0.05 or P〈0.01）. Conclusion： YSC has marked effects in reducing the recurrence of CGN and in decreasing urinary protein, and its mechanism might be related with its function in regulating the ratio of T-lymphocyte subsets to enhance the immunity of patients.

Effectiveness of Qingre Lishi Yishen decoction on the glomerular fibrosis of immunoglobulin A nephropathy in a rat’s model

OBJECTIVE: To investigate the effect of the clinical effective prescription of Qingre Lishi Yishen decoction(QRLS) on the activation of mesangial cells in immunoglobulin A nephropathy(IgAN) rats.METHODS: IgAN rat’s model was established by combine with intragastric administration of bovine serum albumin(BSA) + intravenous injection of lipopolysaccharide(LPS) by + subcutaneous injection of carbon tetrachloride(CCL4). Then the animals were randomly divided into four groups: control group, IgAN model group, IgAN model with Valsartan(Val) treatment group and IgAN model with QRLS treatment group. To observe the indexes of 24-h urine protein, renal function, deposition of immune complexes, expression of activation factor, fibrosis marker and inflammatory cytokines in four different groups.RESULTS: The Val or QRLS treatment group:(a) it reduced the immune complexes deposition of IgA in glomerular mesangial and inhibited mesangial cell proliferation;(b) it decreased the expression of smooth muscle actin(α-SMA), fibronectin(FN) and tumor necrosis factor alpha(TNF-α).CONCLUSION: The study suggested that QRLS ameliorate renal structure and function in IgAN rat’s model. Furthermore, we also observed that QRLS alleviated mesangial cells activation and matrix accumulation partly by decreasing the α-SMA,then to downregulated the expression of FN and TNF-α.

Chinese Medicine Yishen Jiangu Granules(益肾健骨颗粒)on Aromatase Inhibitor-Associated Musculoskeletal Symptoms

Objective： To assess the effectiveness of Yishen Jiangu Granules（益肾健骨颗粒, YSJGG） on aromatase inhibitor-associated musculoskeletal symptoms（AIMSS）. Methods： A single-arm, open-label study was conducted in 34 postmenopausal women with breast cancer who experienced AIMSS. Patients were treated with YSJGG for 12 weeks（12.4 g orally twice daily）. The primary outcome was a change in the mean worst pain score of Brief Pain Inventory-Short Form（BPI-SF） over 12 weeks, and the second outcomes included changes in pain severity and pain-related interference of BPI-SF and Western Ontario and McMaster Universities Osteoarthritis Index（WOMAC）, Modified Score for the Assessment of Chronic Rheumatoid Affections of the Hands（M-SACRAH）, the Functional Assessment of Cancer Therapy-Breast（FACT-B）, bone mineral density（BMD） and blood indices such as calcium（Ca）, phosphate（P）, and alkaline phosphatase（ALP）. Results： Of 37 women recruited, 30 initiated the therapy and 24 were evaluable at 12 weeks. The primary outcome（BPI-SF worst pain scores） achieved a 2.17-point reduction compared with baseline（5.75±1.87 vs 3.58±2.15, P〈0.01）. There were reductions in pain severity（decreased 1.65, P〈0.01） and pain-related interference（decreased 2.55, P〈0.01）. The changes in WOMAC and M-SACRAH scores were similar to BPI-SF（P〈0.05）. In the FACT-B, only physical wel-being and functional wel-being were improved compared with baseline（P〈0.05）. No clinical differences were found in BMD, Ca, P and ALP. Conclusion： YSJGG is an effective and wel-tolerated agent to reduce AIMSS.